The thymus is an unpaired organ located in the mediastinal cavity anterior to and above the heart. It consists of two flattened symmetrical lobes each enclosed in a capsule, from which trabecula extend into the gland dividing each lobe into many lobules, each consisting of a cortex and medulla. The cortex is composed of dense lymphoid tissue containing many immature T cells (thymocytes) closely packed together. The medulla also contains thymocytes, but they are less numerous and more differentiated. These two regions are also characterized by distinct subpopulations of thymic stromal cells, including epithelial cells, macrophages, fibroblasts and dendritic cells. It also contains characteristic thymic Hassall's corpuscles comprised of terminally differentiated medullary epithelial cells.
The thymus is necessary for the development of T cells and T cells are necessary for immunocompetence. For example, children with DiGeorge Syndrome or mice of the nu/nu strain are lacking a thymus and are immunocompromised.
Thymocytes develop in the thymus as the precursor of the thymus-derived lymphocyte (T-lymphocyte) that constitutes the cellular arm of the immune response. The pro-thymocyte migrates from the bone marrow to the thymus where it proliferates and differentiates into thymic lymphoid cells (T cells). Each cell is programmed to recognize a specific foreign antigen by antigen specific T cell receptors (TCR). These cells leave the thymus to circulate in the blood as "long-lived" small and medium-sized lymphocytes with a life-span up to five years. Some settle in lymph nodes and the spleen, specifically the corticomedullary junction of lymph nodes and cuffing the penicilliary arteries in the spleen.
Some antigens, such as proteins from bacteria, viruses, fungi and protozoa can induce a cellular immune response directly. Antigen presenting cells such as macrophages and dendritic cells are considered to be necessary for processing and presenting all antigens to T cells. On initial contact with the antigen, the T cell undergoes clonal proliferation and differentiates into committed T cells with various functions. Abnormalities in the process of T cell differentiation may result in immunodeficiencies, characterized by diminished T cell responses, or autoimmune diseases, characterized by enhanced and unregulated T cell responses.
The activated T-lymphocyte mediates cellular immunity by a direct toxic effect, reacting directly with cell-membrane-associated antigens, or by releasing various soluble factors called lymphokines. Lymphokines are referred to as the chemical mediators of cellular immunity and several factors have now been defined, for example, interferon- (IFN-) which activates macrophage antigen presenting activity and regulates further T cell differentiation and lymphotoxin (LT) which prevents clonal proliferation of lymphocytes and damages lymphocytes and other cell types.
Stem cell precursors become hematopoietic cells, pro-thymocytes, and pro-B cells. Pro-thymocytes migrate to the thymus and develop into T-lymphocytes; pro-B cells become B-lymphocytes, presumably in the bone marrow. Contact with antigen induces lymphocytic differentiation, for this process, T cells may require macrophage participation and some B cells require T-helper cell participation. Both first and later contacts with antigen result in activated T cells or B cells (plasma cells), the mediators respectively, of cellular and of humoral (antibody-mediated) immunity.
Ultimately, T cells control both the cellular and humoral arms of the immune system through the release of factors such as B cell growth factor (interleukin-4, IL-4). The importance of T cells in immunocompetence is evidenced by acquired immunodeficiency disease (AIDS), in which a specific T cell subpopulation is deleted. Therefore, there is a need to identify and characterize proteins which regulate T cell maturation, growth and effector function. Proteins, such as hHSP which are expressed in the thymus, the site where T cells differentiate, have a distinct therapeutic potential in T cell regulation and in the treatment of immunodeficiency, autoimmune disease or other forms of hematopoietic dysfunction.